Infectiousness in a Cohort of Brazilian Dogs: Why Culling Fails to Control Visceral Leishmaniasis in Areas of High Transmission

The elimination of seropositive dogs in Brazil has been used to control zoonotic visceral leishmaniasis but with little success. To elucidate the reasons for this, the infectiousness of 50 sentinel dogs exposed to natural Leishmania chagasi infection was assessed through time by xenodiagnosis with the sandfly vector, Lutzomyia longipalpis. Eighteen (43%) of 42 infected dogs became infectious after a median of 333 days in the field (105 days after seroconversion). Seven highly infectious dogs (17%) accounted for >80% of sandfly infections. There were positive correlations between infectiousness and anti-Leishmania immunoglobulin G, parasite detection by polymerase chain reaction, and clinical disease (logistic regression, r2 = 0.080.18). The sensitivity of enzyme-linked immunosorbent assay to detect currently infectious dogs was high (96%) but lower in the latent period (<63%), and specificity was low (24%). Mathematical modeling suggests that culling programs fail because of high incidence of infection and infectiousness, the insensitivity of the diagnostic test to detect infectious dogs, and time delays between diagnosis and culling

Immune Responses in Human Necatoriasis: Association between Interleukin-5 Responses and Resistance to Reinfection

Cytokine and proliferative responses to Necator americanus infection were measured in a treatment-reinfection study of infected subjects from an area of Papua New Guinea where N. americanus is highly endemic. Before treatment, most subjects produced detectable interleukin (IL)4 (97%), IL-5 (86%), and interferon (IFN)-γ(64%) in response to adult N. americanus antigen. Pretreatment IFN-γ responses were negatively associated with hookworm burden, decreasing by 18 pg/mL for each increase of 1000 eggs/gram (epg) (n = 75; P < .01). Mean IFN-γ responses increased significantly after anthelmintic treatment, from 166 to 322 pg/mL (n = 42; P < .01). The intensity of reinfection was significantly negatively correlated with pretreatment IL-5 responses, decreasing by 551 epg for each 100 pg/mL increase in production of IL-5 (n = 51; P < .01). These data indicate that there is a mixed cytokine response in necatoriasis, with worm burdenassociated suppression of IFN-γ responses to adult N. americanus antigen. Resistance to reinfection is associated with the parasite-specific IL-5 response

Detection of Leishmania infantum by PCR, serology and cellular immune response in a cohort study of Brazilian dogs

The sensitivity and specificity of PCR, serology (ELISA) and lymphoproliferative response to Leishmania antigen for the detection of Leishmania infantum infection were evaluated in a cohort of 126 dogs exposed to natural infection in Brazil. For PCR, Leishmania DNA from bone-marrow was amplified with both minicircle and ribosomal primers. The infection status and time of infection of each dog were estimated from longitudinal data. The sensitivity of PCR in parasite-positive samples was 98%. However, the overall sensitivity of PCR in post-infection samples, from dogs with confirmed infection, was only 68%. The sensitivity of PCR varied during the course of infection, being highest (78–88%) 0–135 days post-infection and declining to around 50% after 300 days. The sensitivity of PCR also varied between dogs, and was highest in sick dogs. The sensitivity of serology was similar in parasite-positive (84%), PCR-positive (86%) and post-infection (88%) samples. The sensitivity of serology varied during the course of infection, being lowest at the time of infection and high (93–100%) thereafter. Problems in determining the specificity of serology are discussed. The sensitivity and specificity of cellular responsiveness were low. These data suggest that PCR is most useful in detecting active or symptomatic infection, and that serology can be a more sensitive technique for the detection of all infected dogs

Tissue Cytokine Responses in Canine Visceral Leishmaniasis

To elucidate the local tissue cytokine response of dogs infected with Leishmania chagasi, cytokine mRNA levels were measured in bone marrow aspirates from 27 naturally infected dogs from Brazil and were compared with those from 5 uninfected control animals. Interferon-γ mRNA accumulation was enhanced in infected dogs and was positively correlated with humoral (IgG1) but not with lymphoproliferative responses to Leishmania antigen in infected dogs. Increased accumulation of mRNA for interleukin (IL)4, IL-10, and IL-18 was not observed in infected dogs, and mRNA for these cytokines did not correlate with antibody or proliferative responses. However, infected dogs with detectable IL-4 mRNA had significantly more severe symptoms. IL-13 mRNA was not detectable in either control or infected dogs. These data suggest that clinical symptoms are not due to a deficiency in interferon-γ production. However, in contrast to its role in human visceral leishmaniasis, IL-10 may not play a key immunosuppressive role in dogs

Competitive formation of spiro and ansa derivatives in the reactions of tetrafluorobutane-1,4-diol with hexachlorocyclotriphosphazene: a comparison with butane-1,4-diol

Reaction of hexachlorocyclotriphosphazene, N3P3Cl6 (1), in two stoichiometries (1:1.2 and 1:3) with the sodium derivative of the fluorinated diol, 2,2,3,3-tetrafluorobutane-1,4-diol, (2), in THF solution at room temperature afforded six products, whose structures have been characterized by X-ray crystallography and 1H, 19F and 31P NMR spectroscopy: the mono-spiro compound, N3P3Cl4(OCH2CF2CF2CH2O), (3), its ansa isomer, (4), a di-spiro derivative N3P3Cl2(OCH2CF2CF2CH2O)2, (5), its spiro-ansa (6) and non-gem cis bis-ansa (7) isomers and a tri-spiro compound N3P3(OCH2CF2CF2CH2O)3, (8). The tri-spiro derivative (8) was also formed in the reaction of the ansa compound (4) with diol (2) in a 1:3 ratio in THF at room temperature. The reactions of (1) with step-wise additions of (2) were also investigated at low temperature (-780C) to give the same range of products as at room temperature. The results of all reactions are compared with previous work on the reactions of (1) with butane-1,4-diol/pyridine mixtures and with the reaction of hexafluorocyclotriphosphazene, N3P3F6 (9), with the silyl derivative of the diol (2), (Me3SiOCH2CF2)2, in a 1:0.4 mole ratio in the same solvent, THF

Stereoisomerism in pentaerythritol-bridged cyclotriphosphazene tri-spiranes: spiro and ansa 1,3-propanediyldioxy disubstituted derivatives

Four isomeric products were isolated and purified from the reaction of 1,3-propanediol with the tetra-spirane cyclophosphazene-organophosphate compound (1): viz. the di-monospiro (2a), di-monoansa (2b) and two monospiro-monoansa derivatives (2c) and (2d). It is shown by 31P NMR spectroscopy on addition of a chiral solvating agent (CSA) that both the di-monospiro (2a) and di-monoansa (2b) derivatives are racemates, as expected, whereas no splitting of NMR signals occurred on addition of CSA to solutions of (2c) and (2d). It is found by X-ray crystallography that the two monospiro-monoansa spirane derivatives, (2c) and (2d), are meso diastereoisomers, which represent a new case of the stereochemistry of bis di-substituted cyclophosphazene derivatives of (1). It is also observed from the 31P NMR spectrum of the reaction mixture, supported by the yields of pure compounds, that formation of a spiro group is about 4.5 times more likely than that of an ansa moiety under the conditions of the reaction

Epidemiology and integrated control of Potato Late Blight in Europe

Phytophthora infestans, the causal agent of late blight, is a major threat to potato production in northwestern Europe. Before 1980, the worldwide population of P. infestans outside Mexico appeared to be asexual and to consist of a single clonal lineage of A1 mating type characterized by a single genotype. It is widely believed that new strains migrated into Europe in 1976 and that this led to subsequent population changes including the introduction of the A2 mating type. The population characteristics of recently collected isolates in NW Europe show a diverse population including both mating types, sexual reproduction and oospores, although differences are observed between regions. Although it is difficult to find direct evidence that new strains are more aggressive, there are several indications from experiments and field epidemics that the aggressiveness of P. infestans has increased in the past 20 years. The relative importance of the different primary inoculum sources and specific measures for reducing their role, such as covering dumps with plastic and preventing seed tubers from becoming infected, is described for the different regions. In NW Europe, varieties with greater resistance tend not to be grown on a large scale. From the grower’s perspective, the savings in fungicide input that can be achieved with these varieties are not compensated by the higher (perceived) risk of blight. Fungicides play a crucial role in the integrated control of late blight. The spray strategies in NW Europe and a table of the specific attributes of the most important fungicides in Europe are presented. The development and use of decision support systems (DSSs) in NW Europe are described. In The Netherlands, it is estimated that almost 40% of potato growers use recommendations based on commercially available DSS. In the Nordic countries, a new DSS concept with a fixed 7-day spray interval and a variable dose rate is being tested. In the UK, commercially available DSSs are used for c. 8% of the area. The validity of Smith Periods for the new population of P. infestans in the UK is currently being evaluated

Blueprints for Green Communities: Climate change visioning and participatory landscape planning for resilient low-carbon communities

Emerging 3D visualization tools and future visioning methods offer new ways to make climate change impacts and potential responses explicit, and accelerate holistic solutions. Previous research at UBC’s Collaborative for Advanced Landscape Planning (CALP) and elsewhere confirms that 4D visioning processes using landscape visualizations of recognizable places under alternative future conditions can improve community engagement and awareness on complex environmental and planning issues (Tress and Tress, 2002; Sheppard and Meitner, 2005; Schroth, 2007). This paper examines a visioning process (Sheppard, 2008) that applies visualization and other landscape planning methods to explore high and low-carbon futures of the affluent, sub-urban hillside community of North Vancouver with climate change, and its surrounding scenic North Shore sub region of Metro Vancouver, BC, Canada

An investigation into the inactivation kinetics of hydrogen peroxide vapor against clostridium difficile endospores

C. difficile spores are resistant to routine cleaning agents and are able to survive on inanimate surfaces for long periods of time. There is increasing evidence of the importance of the clinical environment as a reservoir for pathogenic agents and as a potential source of healthcare-associated infections (HCAIs). In this context, to reduce the risk of cross-transmission, terminal disinfection of hospital wards and isolation rooms using hydrogen peroxide vapor (HPV) is attracting attention. Spores of C. difficile (ribotype 027) were exposed to constant concentrations of HPV ranging between 11 and 92 mg m−3 (ppm) for a range of exposure times in a specially designed chamber. The inactivation data thus obtained was fitted using the modified Chick–Watson inactivation model to obtain decimal reduction values (D values). D values ranged from 23 to 1.3 min at HPV concentrations of 11 and 92 ppm, respectively. We present a simple mathematical model based on the inactivation kinetic data obtained here to estimate the efficacy of commercial HPV processes used in healthcare environmental decontamination. C. difficile spores showed linear inactivation kinetics at steady HPV concentrations ranging between 10 and 90 ppm. The data obtained here was used to provide estimates of the inactivation efficacy of commercial HPV process cycles, which employ unsteady HPV concentrations during the decontamination process

ICAM- melanoma cells are relatively resistant to CD3-mediated T-cell lysis

Abstract The primary activation pathway of T cells is via the T-cell receptor (TCR)/CD3 complex, which is functionally interrelated with various accessory molecules. We examined the contribution of the lymphocyte-function-associated antigenI/intercellular adhesion molecule I (LFA-I/ICAM-I) interaction to CD3/TCR-mediated lysis by cytotoxic T lymphocytes (CTL). We used ICAM-I-or+ tumor cell lines as target cells and anti-CD3- or anti-LFA-I containing hetero-cross-linked monoclonal antibody (MAb) to bridge CTL and target cells and simultaneously to activate CTL. The ICAM-I- melanoma-derived cell line lgR39 was relatively resistant to CD3-mediated lysis by both TCRαβ+ and TCRγdL+ CTL, when compared with ICAM-I+ cell lines. Induction of ICAM-I on the membrane of lgR39 cells by tumor necrosis factor (TNF) rendered these cells more susceptible to CD3-mediated lysis. Anti-ICAM-I MAb inhibited this TNF-enhanced susceptibility to lysis, directly demonstrating that the induction of ICAM-I was critical in the TNF-induced increase in susceptibility to lysis of lgR39 cells. CTL formed less efficient conjugates with the ICAM-I- cells as compared to ICAM-I+ cells. Both spontaneous and CD3-induced conjugate formation as well as CD3-mediated lysis of ICAM-I- tumor cells by CTL were enhanced by the addition of anti-LFA-I containing heterocross-linked MAb, thereby mimicking the LFA-I/ICAM-I interaction between CTL and target cells. Soluble anti-CD18 MAb inhibited CD3-mediated lysis of ICAM-I- target cells by CTL without affecting their conjugate formation. Anti-LFA-I MAb added after conjugate formation still inhibited lysis of both ICAM-I+or- tumor cells. Taken together, these findings suggest that the LFA-I/ICAM-I interaction co-activates CD3/TCR-mediated lysis by CTL through both an enhanced CTL-target cell binding and the delivery of post-conjugate costimulatory signals